CTLA-4 gene A/G polymorphism associated with diabetes mellitus in Han Chinese

Objective To investigate the association of cytotoxic T lymphocyte-associated antigen 4 ( CTLA-4) gene A/G polymorphism with susceptibility to diabetes mellitus in Han C hinese.Methods An A/G transition at position 49 of exon 1 was analyzed in 31 patients with type 1 diabetes, 31 patients with type 2 diabetes, and 36 controls were analyzed by polymerase chain reaction-restriction fragment length polymorphism analysis. Results A highly significant increase in the frequency of the G allele was seen in patie nts with type 1 diabetes compared with controls (66.1% vs. 34.7%, respectivel y; P <0.0005; OR=3.670). This reflected an increase in the GG genotype in patients (48.4% vs. 22.2%, respectively; P =0.025; OR=3.281) and a signi ficant decrease in the AA genotype (16.1% vs. 52.8%, respectively; P =0.0 02). The allele frequencies of A and G in patients with type 2 diabetes were no t significantly different from controls (A/G, 50.0/50.0% vs. 65.3/34.7%; P =not significant). The distribution of genotype, however, differed significa ntly. This difference reflected an increase in the AG genotype in patients (54 .8% vs. 25.0%, respectively; P =0.012; OR=3.643) and a decrease in the A A genotype (22.6% vs. 52.8%, respectively; P =0.011). Conclusions CTLA-4 49 AA is protective from diabetes mellitus, whereas, CTLA-4 49 G allele (both as homozygotes and as heterozygotes ) confers an increased risk of diabet es mellitus.